Green fluorescent proteins (GFPs) for measuring voltage

Siegel, M.S., Isacoff, E.Y. 2010, Cold Spring Harbor Protocols

Abstract

Measuring signal transduction in large numbers of cells, with high spatial and temporal resolution, is a fundamental problem for studying information processing in the nervous system. To address this problem, a family of detectors that are chimeras between signal transduction proteins and fluorescent proteins has been designed. The prototype sensor is a genetically encoded probe that can be used to measure transmembrane voltage in single cells. This article describes a modified green fluorescent protein (GFP), fused to a voltage-sensitive K+ channel, so that voltage-dependent rearrangements in the K+ channel induce changes in the fluorescence of GFP. The probe has a maximal fractional fluorescence change of 5.1%, making it comparable to some of the best organic voltage-sensitive dyes. Moreover, the fluorescent signal is expanded in time in a manner that makes the signal 30-fold easier to detect than a traditional linear dye. DNA-encoded sensors have the advantage that they may be introduced into an organism noninvasively and targeted to specific brain regions, cell types, and subcellular compartments.